Emerging and state of the art hemagglutinin-targeted influenza virus inhibitors.

Zhang, Grace; Liang, Taizhen; Nandakumar, Kutty Selva; Liu, Shuwen

doi:10.1080/14656566.2020.1856814

Cited by 22 publications

(14 citation statements)

References 144 publications

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“…Therefore, additional studies are required to address the detailed mechanisms underlying the local production of IgT-specific responses in the SB mucosa. It is also worth noting that influenza hemagglutinin-specific IgA is produced locally in the mice lung tissue 58 – 60 .…”

Section: Discussionmentioning

confidence: 99%

Teleost swim bladder, an ancient air-filled organ that elicits mucosal immune responses

Huang

Kong

et al. 2022

Cell Discov

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The air-filled organs (AOs) of vertebrates (lungs and swim bladders) have evolved unique functions (air-breathing or buoyancy control in water) to adapt to different environments. Thus far, immune responses to microbes in AOs have been described exclusively in the lungs of tetrapods. Similar to lungs, swim bladders (SBs) represent a mucosal surface, a feature that leads us to hypothesize a role for SB in immunity. In this study, we demonstrate that secretory IgT (sIgT) is the key SB immunoglobulin (Ig) responding to the viral challenge, and the only Ig involved in viral neutralization in that organ. In support of these findings, we found that the viral load of the SB from fish devoid of sIgT was much higher than that of control fish. Interestingly, similar to the lungs in mammals, the SB represents the mucosal surface in fish with the lowest content of microbiota. Moreover, sIgT is the main Ig class found coating their surface, suggesting a key role of this Ig in the homeostasis of the SB microbiota. In addition to the well-established role of SB in buoyancy control, our findings reveal a previously unrecognized function of teleost SB in adaptive mucosal immune responses upon pathogenic challenge, as well as a previously unidentified role of sIgT in antiviral defense. Overall, our findings indicate that despite the phylogenetic distance and physiological roles of teleost SB and mammalian lungs, they both have evolved analogous mucosal immune responses against microbes which likely originated independently through a process of convergent evolution.

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Section: Discussionmentioning

confidence: 99%

Teleost swim bladder, an ancient air-filled organ that elicits mucosal immune responses

Huang

Kong

et al. 2022

Cell Discov

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“…Till now, a series of small protein or peptide viral fusion inhibitors targeting conserved epitopes of HA stem have been developed, such as HB36 and HB80 (19), HB36.3 and HB80.4 (23), HB36.6 (21), JNJ4796 (22), P7 (20). Some of these inhibitors have been shown to protect mice from influenza virus infection, such as HB36.6 and JNJ4796 (21,22), and four antibody drugs (CR6261, 39.29, CR8020 and MEDI8852) have entered phase II clinical trial (136)(137)(138). In addition, several universal vaccines based on the HA stem, such as headless HA and HA mini-stems, have also shown promising prospects, and chimeric HA has entered phase I clinical trial (136,137).…”

Section: Epitopes Of the Hydrophobic Groove Regionmentioning

confidence: 99%

Analysis of the conserved protective epitopes of hemagglutinin on influenza A viruses

Jiao

Wang²,

Chen³

et al. 2023

Front. Immunol.

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The conserved protective epitopes of hemagglutinin (HA) are essential to the design of a universal influenza vaccine and new targeted therapeutic agents. Over the last 15 years, numerous broadly neutralizing antibodies (bnAbs) targeting the HA of influenza A viruses have been isolated from B lymphocytes of human donors and mouse models, and their binding epitopes identified. This work has brought new perspectives for identifying conserved protective epitopes of HA. In this review, we succinctly analyzed and summarized the antigenic epitopes and functions of more than 70 kinds of bnAb. The highly conserved protective epitopes are concentrated on five regions of HA: the hydrophobic groove, the receptor-binding site, the occluded epitope region of the HA monomers interface, the fusion peptide region, and the vestigial esterase subdomain. Our analysis clarifies the distribution of the conserved protective epitope regions on HA and provides distinct targets for the design of novel vaccines and therapeutics to combat influenza A virus infection.

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“…The highly conserved HA stem, which produces protective antibodies that neutralize viral infectivity without inhibiting hemagglutination, is a more attractive target for the development of a universal influenza vaccine. Many studies have shown that this site contains many antigenic epitopes that bind broad-spectrum neutralizing antibodies (bnAbs) and has an important role in inhibiting viral entry into cells [ 34 , 35 , 36 , 37 ].…”

Section: Development Of Universal Influenza Vaccinementioning

confidence: 99%

Influenza and Universal Vaccine Research in China

Zhang

et al. 2022

Viruses

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Influenza viruses usually cause seasonal influenza epidemics and influenza pandemics, resulting in acute respiratory illness and, in severe cases, multiple organ complications and even death, posing a serious global and human health burden. Compared with other countries, China has a large population base and a large number of influenza cases and deaths. Currently, influenza vaccination remains the most cost-effective and efficient way to prevent and control influenza, which can significantly reduce the risk of influenza virus infection and serious complications. The antigenicity of the influenza vaccine exhibits good protective efficacy when matched to the seasonal epidemic strain. However, when influenza viruses undergo rapid and sustained antigenic drift resulting in a mismatch between the vaccine strain and the epidemic strain, the protective effect is greatly reduced. As a result, the flu vaccine must be reformulated and readministered annually, causing a significant drain on human and financial resources. Therefore, the development of a universal influenza vaccine is necessary for the complete fight against the influenza virus. By statistically analyzing cases related to influenza virus infection and death in China in recent years, this paper describes the existing marketed vaccines, vaccine distribution and vaccination in China and summarizes the candidate immunogens designed based on the structure of influenza virus, hoping to provide ideas for the design and development of new influenza vaccines in the future.

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Emerging and state of the art hemagglutinin-targeted influenza virus inhibitors.

Cited by 22 publications

References 144 publications

Teleost swim bladder, an ancient air-filled organ that elicits mucosal immune responses

Teleost swim bladder, an ancient air-filled organ that elicits mucosal immune responses

Analysis of the conserved protective epitopes of hemagglutinin on influenza A viruses

Influenza and Universal Vaccine Research in China

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